Relationship between achieved LDL-C and saphenous vein graft patency: a post hoc analysis of the NEWTON-CABG CardioLink-5 study

AIMS: In the NEWTON-CABG CardioLink-5 trial, treatment with the PCSK9 inhibitor evolocumab did not improve saphenous vein graft (SVG) patency relative to placebo in post-CABG patients. This post hoc analysis investigated whether achieved month 3 LDL-C levels were related to subsequent measures of SVG patency. METHODS: Adults (≥18 years) on moderate- to high-intensity statins and undergoing CABG surgery with ≥2 SVGs were randomized 3-21 days postoperatively to subcutaneous evolocumab 140 mg or placebo every two weeks for 24 months. The primary endpoint was the proportion of SVGs with ≥50% occlusion on coronary computed tomography angiography or clinically indicated invasive angiography at 24 months. Secondary efficacy outcomes included the proportion of totally occluded SVGs, proportion of participants with ≥1 totally occluded SVG, and SVG total plaque volume. RESULTS: A total of 1198 SVGs were assessed (499 evaluable participants). Mean LDL-C was 2.04 mmol/L and 1.03 mmol/L at baseline and month 3, respectively. Month 3 LDL-C (odds ratio [OR] = 0.74 per 1 mmol/L decrement; P = 0.005) and LDL-C change from baseline to month 3 (OR = 0.78 per 1 mmol/L decrease; P = 0.03) were related to the primary endpoint, with lower achieved levels or greater reductions associated with improved vein outcomes. These relationships did not depend on treatment assignment (Pinteraction = 0.79 and 0.84, respectively). CONCLUSION: LDL-C achieved over the range in this study was associated with SVG-related angiographic outcomes, suggesting LDL-C may have some role in SVG patency. These findings emphasize the importance of adhering to cholesterol guidelines after CABG.